Time rate of blood pressure variation is associated with increased common carotid artery intima-media thickness

The extent of target-organ damage has been positively associated with the magnitude of blood pressure (BP) variability in essential hypertension. However, the clinical implications of the rate of BP changes have never been investigated. We evaluated the association between the rate of systolic BP (SBP) variation derived from ambulatory BP monitoring (ABPM) data analysis and the extent of common carotid artery (CCA) intima-media thickness (IMT) in normotensive (n=280) and in uncomplicated hypertensive subjects (n=234). The 24-hour rate of SBP variation was significantly (P<0.001) higher in hypertensive (0.608 mm Hg/min; 95% confidence interval [CI], 0.595 to 0.622) than in normotensive individuals (0.567 mm Hg/min; 95% CI, 0.555 to 0.578), even after adjusting for baseline characteristics, day-night BP changes, 24-hour heart rate (HR), SBP, and HR variability. In the entire group of patients, multiple linear regression models revealed independent determinants of CCA-IMT in the following rank order: age (P<0.001), 24-hour rate of SBP variation (P<0.001), male gender (P=0.004), cholesterol (P=0.009), and smoking (P=0.014). A 0.1 mm Hg/min increase in the 24-hour rate of SBP variation was associated to an increment of 0.029 mm (95% CI, 0.018 to 0.040) in CCA-IMT independent of BP and HR levels, BP and HR variability, and dipping status. The rate of SBP variation during the morning BP surge correlated independently (P<0.001) to larger CCA-IMT values after adjustment for baseline characteristics and other ABPM parameters. Thus, the rate of BP fluctuations is greater in hypertensive patients and correlates to increased CCA-IMT. This finding indicates that steeper BP variations may produce a greater stress on the vessel wall and consequently result in medial hypertrophy of the large arteries.     

Carotid plaques, but not common carotid intima-media thickness, are independently associated with aortic stiffness.

OBJECTIVE: It has been suggested that non-invasive aortic stiffness measurements can be used as an indicator of atherosclerosis. The relationships of arterial stiffness with arterial wall hypertrophy and atherosclerosis however, have rarely been investigated in large-scale studies. The present study reports the associations of carotid arterial structure assessed by B-mode ultrasound with carotid-femoral pulse-wave velocity in hypertensive and non-hypertensive subjects. DESIGN AND METHODS: Free health examinations were performed on 564 subjects (age 58.2 +/- 10.8 years, 31.9% of women, 53.2% of all were hypertensive). Carotid-femoral pulse-wave velocity (PWV) was used to assess aortic stiffness. Carotid ultrasound examination included measurements (at sites free of plaques) of intima-media thickness (IMT) at the common carotid arteries (CCA), CCA-lumen diameter, and assessment of atherosclerotic plaques in the extracranial carotid arteries. RESULTS: Subjects with carotid plaques had significantly higher mean sex-adjusted values of PWV than those without carotid plaques (12.7 +/- 0.2 versus 11.1 +/- 0.1 m/s, P < 0.001). Multivariate analyses showed that this association was independent of sex, age, height, body mass index, mean blood pressure, pulse pressure, diabetes, hypercholesterolaemia and smoking habits (P < 0.009). PWV was positively associated with CCA-IMT and CCA-lumen diameter in sex-adjusted analysis (partial correlation coefficients (r ) were respectively 0.39 and 0.42, P < 0.001 for each). However, the association of PWV with CCA-IMT, but not that with CCA-lumen diameter, disappeared after further adjustment for age and blood pressure measurements (mean blood pressure and/or pulse pressure). CONCLUSION: This study shows that there is a differential association of PWV with CCA-IMT and carotid plaques. The nature of the independent positive association between atherosclerosis and arterial stiffness should be thoroughly investigated.     

Interleukin-2 levels are associated with carotid artery intima-media thickness

OBJECTIVE: To show that serum interleukin levels are associated with carotid intima-media thickness (IMT). BACKGROUND: Inflammation is hypothesized to play a central role in atherogenesis, and serum markers of inflammation are predictive of cardiovascular disease. Interleukin-2, a pro-inflammatory cytokine produced largely by naive CD4 T cells and Th1 (pro-inflammatory) T cells, has been found in a high proportion of carotid plaques. METHODS: High-resolution ultrasound of the carotid arteries and serum cytokine levels were measured in stroke-free participants. The mean of the maximum IMT in bilateral bifurcation, common and internal carotid artery segments was measured. Serum levels of interleukin (IL)-1beta, IL-2, IL-6, C-reactive protein, tumor necrosis factor (TNF) alpha and TNF receptors were measured using enzyme-linked immunosorbent assay. RESULTS: IL-2 levels were significantly correlated with IMT (r=0.33, P<0.0001), but other cytokines were not. Each unit increase in IL-2 was significantly associated with a mean increase in IMT of 0.18 mm (P=0.0001). After adjusting for other atherosclerotic risk factors, the association was unchanged (mean increase in IMT per unit increase IL-2=0.18 mm, P<0.0001). Each standard deviation increase in the level of IL-2 was associated with an increased risk (adjusted odds ratio 1.80, 95% CI 1.12-2.89) for an IMT> or =1.0mm (75th percentile for IMT). CONCLUSION: Serum levels of IL-2, a pro-inflammatory cytokine, are associated with carotid artery IMT, a predictor of stroke and vascular disease. Serum inflammatory markers may provide a novel marker of atherosclerotic risk, and inflammation may provide a new therapeutic target for stroke prevention.     

Low plasma lycopene concentration is associated with increased intima-media thickness of the carotid artery wall

Although a number of epidemiological studies have evaluated the association between ss-carotene and the risk of cardiovascular diseases, there has been little research on the role of lycopene, an acyclic form of ss-carotene, with regard to the risk of cardiovascular disease. We investigated the relationship between plasma concentrations of lycopene and intima-media thickness of the common carotid artery wall (CCA-IMT) in 520 middle-aged men and women (aged 45 to 69 years) in eastern Finland. They were examined from 1994 to 1995 at the baseline of the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study, a randomized trial concerning the effect of vitamin E and C supplementation on atherosclerotic progression. The subjects were classified into 2 categories according to the median concentration of plasma lycopene (0.12 micromol/L in men and 0.15 micromol/L in women). Mean CCA-IMT of the right and left common carotid arteries was 1.18 mm in men and 0.95 mm in women with plasma lycopene levels lower than the median and 0.97 mm in men (P:<0.001 for difference) and 0.89 mm in women (P:=0.027 for difference) with higher levels of plasma lycopene. In ANCOVA adjusting for cardiovascular risk factors and intake of nutrients, in men, low levels of plasma lycopene were associated with a 17.8% increment in CCA-IMT (P:=0.003 for difference). In women, the difference did not remain significant after the adjustments. We conclude that low plasma lycopene concentrations are associated with early atherosclerosis, manifested as increased CCA-IMT, in middle-aged men living in eastern Finland.     

Carotid artery intima-media thickness is associated with coronary artery disease

OBJECTIVE: The intima-media thickness (IMT) of the carotid artery is dependent on the risk factor load during life and correlates well with the degree of atherosclerosis, also in other vascular beds. METHODS: We reviewed our database of IMT measurements, from January 2002 to February 2007. We compared the mean IMT values of patients without a history of coronary artery disease (group 1) with those with a history of coronary artery disease (group 2). For both groups we divided the results of measurements according to age. We compared the IMT between both groups and looked for a correlation with increasing age. The IMT was measured with high-resolution echography at the posterior wall of the common carotid artery, using an automated edge-tracking method. RESULTS: The database contained 598 IMT measurements in group 1 and 672 in group 2. In both groups we observed a significant increase in IMT with increasing age. Within a certain age group, a significant difference in IMT between group 1 and 2 occurred at an age of 40 years or above (age 40-65: IMT 645.54 versus 671.71 microm, respectively, P = 0.04, and age > 65 years: IMT 715.2 versus 772.91 microm, respectively, P = 0.01). CONCLUSIONS: IMT increases with age and is higher in patients with a history of vascular disease. This difference is significant in patients of 40 years or older. This finding supports the recommendations of the prevention conference of the American Heart Association, that carefully performed IMT measurement can add incremental information to traditional risk factor assessment in asymptomatic individuals above the age of 45 years.     

High-resolution radial artery intima-media thickness and cardiovascular risk factors in patients with suspected coronary artery disease--comparison with common carotid artery intima-media thickness

ObjectiveThe radial artery wall structure can be measured with non-invasive very high-resolution ultrasound with great feasibility and high accuracy. In the present study, we aim to explore clinical correlates of radial artery intima-media thickness (rIMT), in a relatively large patient cohort with suspected coronary artery disease, and further compare those to common carotid artery IMT (cIMT) that is an accepted surrogate marker of atherosclerosis.MethodsFour hundred and sixteen patients referred to myocardial perfusion scintigram (MPS) were recruited, and cIMT and rIMT were scanned using conventional and very high-resolution ultrasound (55 MHz transducer), respectively. A number of plasma biomarkers were also measured.ResultsBoth cIMT and rIMT were similarly correlated with disease history, MPS-verified ischemia, carotid plaque burden, and lipid status. Repeated measurement of rIMT showed acceptable variability.ConclusionRadial artery IMT may constitute a novel feasible imaging biomarker for systemic atherosclerosis burden, which may be used in future imaging trials to evaluate, e.g. anti-atherosclerotic treatments.     

Increased carotid artery intima-media thickness is associated with a novel mutation of low-density lipoprotein receptor independently of major cardiovascular risk factors

The current study sought to investigate the role of low-density lipoprotein receptor (LDLr) mutations in assessing the risk profile of familial hypercholesterolemia (FH) patients, independently of major cardiovascular risk factors. FH due to LDLr mutations is associated with premature atherosclerosis. The variable clinical severity of the disease in heterozygotes has been related to cholesterol levels and the coexistence of other cardiovascular risk factors, but the independent role of different LDLr mutations is still unclear. cDNA of LDL gene was sequenced in 102 patients with clinical features of heterozygous FH. Carotid artery intima-media thickness (IMT) was measured by B-mode ultrasound imaging in all patients. Sixteen different mutations (5 never described) were found in 82 patients (49 families; mean age, 39 years; 53% women). One of the newly described mutations, the 2312-3 C-->A, was found in 24 patients (13 families). The mean of maximum thicknesses was significantly higher in the 2312-3 C-->A group than in patients with other LDLr mutations (P=.004 after adjustment for major cardiovascular risk factors). Similar results (P=.001) were obtained in the adjusted comparisons of probands only, and of the patients with similar baseline cholesterol (P=.002). This study indicates that the identification of an LDLr mutation can help to assess the risk profile of FH patients independently of the major cardiovascular risk factors.     

颈总动脉内膜-中膜厚度及粥样斑块与冠心病的关系

目的:研究颈总动脉内膜-中膜厚度(CIMT)及粥样斑块检出率与冠心病发病及冠脉病变严重程度的关系。方法:114例具有至少一项冠心病危险因素的患者,按冠状动脉造影结果分为冠心病组(70例)和对照组(44例),测定所有病例的双侧CIMT、颈总动脉内径和颈总动脉粥样斑块情况。结果:两组间各项冠心病危险因素均无显著差异。超声结果显示,冠心病组CIMT、粥样斑块检出率均显著增高(P&lt;0.01),颈总动脉内径略增大,但差异不显著。CIMT≥0.8mm和检出粥样斑块为预测冠心病发病的独立指标(P&lt;0.01)。CIMT和粥样斑块检出率均与冠脉病变严重程度呈正相关,在控制了多项影响因素后,相关性仍显著。结论:CIMT增厚、粥样斑块检出为冠心病发病的独立预测因素,并且与冠脉病变严重程度正相关。     

Increased carotid intima-media thickness is associated with higher SYNTAX score

The main purpose of this study was to investigate the relation between carotid intima-media thickness (CIMT) and coronary artery disease (CAD) complexity. Consecutive patients (n = 360) with CAD confirmed by coronary angiography were enrolled. Mean CIMT and the overall SYNTAX score (SXscore) were 0.87 ± 0.12 mm and 15 ± 9, respectively. In univariate analysis, there was a significant correlation between the overall SXscore and CIMT (r = .42, P < .001), age (r = .23, P < .001), hypertension (r = .27, P = 0.001), diabetes (r = 0.11, P = 0.02), smoking (r = .24, P = .01), dyslipidemia (r = .2, P = 0.03), and β-blocker use (r = .19, P < .001). In multivariate analysis, CIMT (β = .34, P < .001) and age (β = .11, P < .019) were independently associated with SXscore. We have demonstrated a significant relation between CIMT and SXscore. Although this study is correlative and no causative conclusions can be drawn, our findings suggest that increased CIMT could reflect complex coronary artery lesions.     

Assessment of local differences in intima-media thickness in the human common carotid artery.

Intimal thickening may be focal in nature and is especially found in areas with low shear rate. To be able to study the relation between intima-media thickness (IMT) and wall shear rate appropriately, a method to assess IMT locally is required. It was the aim of the present study to investigate the ability of a recently developed automated method to assess local differences in IMT, if any, in relatively short arterial segments. Therefore, intrasession interlocation differences in IMT were assessed at the posterior wall of the common carotid artery close to the bulb (0 mm) and 10 and 20 mm more upstream in terms of mean difference +/- 2 standard deviations. Prior to this study we investigated the ability of the system to reproducibly assess IMT locally (intersession intralocation) in terms of repeatability coefficient (= 2 standard deviations). The measurements were performed in the common carotid artery 20 mm proximal to the bulb. The study was performed on young and older subjects presumed to be healthy. The intersession intralocation repeatability coefficient was 0.07 mm in the young group and 0.11 mm in the older group. The IMT close to the bulb (0 mm) was significantly larger (+/-0.050-0.065 mm) than that at the other locations in both age groups. We conclude that local IMT can be assessed reproducibly and local differences in wall morphology in short arterial segments can be studied reliably.     

Flow-dependent vasomotor dysfunction of the popliteal artery related to common carotid artery intima-media thickness

This study was designed to assess a possible correlation between flow-mediated endothelium-dependent vasodilation in the popliteal artery and the intima-media thickness of the common carotid artery. Impaired vasodilation is one of early markers of atherosclerosis that has not been studied on the popliteal artery. An increase in intima-media thickness of the common carotid artery is also considered to be an indication of early stages of atherosclerosis. With use of ultrasound, the diameter of the popliteal artery was measured at rest and during reactive hyperemia after 5-minute arterial occlusion. Subsequently, the intima-media thickness was measured in left common carotid arteries in 27 patients with hyperlipidemia, in 10 patients with confirmed coronary artery disease, and in 20 healthy individuals. In healthy individuals, popliteal artery diameter increased by mean of 6.6 +/- 3.5% (p < 0.01) in relation to hyperemia. In patients with hyperlipidemia before therapy and in patients with coronary disease, no increase in diameter occurred (mean, 0.44% and -1.6%, respectively). The difference between healthy individuals and patients was statistically significant at p < 0.001. The popliteal artery seems to respond similarly to the brachial artery. When comparing the change in popliteal artery diameter and intima-media thickness of common carotid arteries, a strong negative correlation (r = -0.5713, p < 0.001) was observed in all subjects.     

颈总动脉内膜-中膜厚度及粥样斑块与冠心病的关系

目的:研究颈总动脉内膜-中膜厚度(CIMT)及粥样斑块检出率与冠心病发病及冠脉病变严重程度的关系。方法:114例具有至少一项冠心病危险因素的患者,按冠状动脉造影结果分为冠心病组(70例)和对照组(44例),测定所有病例的双侧CIMT、颈总动脉内径和颈总动脉粥样斑块情况。结果:两组间各项冠心病危险因素均无显著差异。超声结果显示,冠心病组CIMT、粥样斑块检出率均显著增高(P<0.01),颈总动脉内径略增大,但差异不显著。CIMT≥0.8mm和检出粥样斑块为预测冠心病发病的独立指标(P<0.01)。CIMT和粥样斑块检出率均与冠脉病变严重程度呈正相关,在控制了多项影响因素后,相关性仍显著。结论:CIMT增厚、粥样斑块检出为冠心病发病的独立预测因素,并且与冠脉病变严重程度正相关。     

Platelet number is negatively and independently associated with carotid intima-media thickness in apparently healthy overweight/obese subjects

Background and Aim

A significant change of platelet number may be a risk factor for atherosclerotic cardiovascular disease. The aim of this study was to investigate the association between platelet number and early signs of atherosclerosis, evaluated by carotid intima-media thickness (c-IMT), in a apparently healthy population mainly represented by obese subjects.

血清瘦素与颈动脉内膜-中层厚度关系的探讨

目的：探讨血清瘦素水平与颈动脉内膜—中层厚度(IMT)的相关关系以及瘦素在动脉粥样硬化发生发展中的作用。方法：选择门诊体检正常者56例,分别测定其血清瘦素、空腹血糖、血脂含量,血压及体重指数(BMI)、腰围,同时使用高分辨率超声检测双侧颈动脉 IMT。结果：颈动脉 IMT 与血清瘦素浓度呈显著正相关(男 r=0.41, P＜0.005,女 r=0.44,P＜0.001),与 BMI、腰围、年龄、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、男性收缩压(SBP)及女性舒张压(DBP)呈正相关(r=0.33～0.51,P＜0.05或＜0.001),剔除 BMI 后 IMT 后仍与瘦素呈正相关(r=0.43,P＜0.001)。结论：血清瘦素浓度与颈动脉 IMT 独立相关,提示瘦素可能有加速动脉粥样硬化发展的作用。     

老年高血压病患者血清瘦素水平与颈动脉内膜中层厚度的相关性

目的 探讨老年高血压病患者血清瘦素(Leptin)与颈动脉内膜中层厚度(IMT)的关系。方法 选取60岁以上老年高血压病患者111例为研究对象,进行血压、血糖、血脂、血清瘦素的测定并测定腰臀比(WHR)计算体质量指数（BMI）,使用高分辨率超声检测双侧颈动脉IMT,把研究对象按IMT分为两组:IMT<1.0 mm(n=54)组和IMT≥1.0 mm(n=57)组,比较两组的差异,并进行相关性分析。结果 IMT≥1.0 mm组年龄、体质量、BMI、SBP、WHR、Leptin、TC、TG、HDL-C、LDL-C均显著高于IMT<1.0 mm组,leptin与IMT具有相关性(r=0.85,P<0.01)。结论 老年高血压病患者leptin与IMT明显相关。     

Thyroid function is associated with carotid intima-media thickness in euthyroid subjects

To investigate the relationship between thyroid function and carotid intima-media thickness (CIMT) in a relatively large general population with euthyroid status we initially enrolled 1772 Japanese adults (421 men and 1351 women) who participated in a medical screening program for the general population over 40 years old. To evaluate only euthyroid subjects without vascular diseases and/or its major risk factors, 1129 were excluded and 643 participants (175 men and 468 women) were included for further analysis. Simple and multivariate linear regression analyses were performed to evaluate free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels and other existing parameters, including carotid intima-media thickness. By multivariate linear regression analysis adjusted for age and sex, free thyroxine was significantly correlated with triglycerides (beta=0.07, p=0.015), carotid intima-media thickness (beta=-0.091, p=0.049), and thyroid-stimulating hormone (beta=-0.091, p=0.003). Thyroid-stimulating hormone was significantly correlated with high-density lipoprotein cholesterol (HDL-C) (beta=-0.001, p=0.015), HbA(1c) (beta=0.038, p=0.045), carotid intima-media thickness (beta=0.27, p=0.001), and free thyroxine (beta=-0.15, p=0.003). When adjusted for confounding factors, free thyroxine was significantly correlated only with carotid intima-media thickness (beta=-0.13, p=0.043) and thyroid-stimulating hormone was significantly correlated with HDL-C (beta=-0.001, p<0.001), HbA(1c) (beta=0.04, p=0.021), and carotid intima-media thickness (beta=0.29, p=0.001). We have demonstrated that carotid intima-media thickness is independently associated with thyroid function within the normal reference range, which suggests an increased cardiovascular risk in subjects with low normal thyroid function.